Annual epidemics and pandemics of influenza (flu) cause significant disease burden and excess mortality due to complications globally. Vaccination with flu vaccine is considered to be the most effective way to alleviate disease burden and mortality caused by influenza, as well as to prevent future pandemics in humans. Currently there are two types of flu vaccines in the market, split vaccines and cold-adapted attenuated vaccines. Pitfalls from both vaccines have long been recognized. Current split flu vaccines have low immunogenicity and cannot be ready in a short timeframe in response to the rapidly emerging strains, such as the H1N1 strain, which caused the 2009 pandemic. Poor immunogenicity has been well known for the split vaccine, in particular among old adults and young children. On the other hand, cold attenuated vaccines are only allowed for use in people between 2 to 49 years old. These problems have limited the benefits of flu vaccines for the population that needs them most. The quick production of low cost, abundant, and effective vaccines (capable of inducing a more robust immune response) is ideal for intervention and prevention of influenza, particularly seasonal influenza in young children and the elderly.
Since the emergence of human infections with avian H5N1 virus in Hong Kong in 1997, human infections with other subtypes of avian influenza virus, including H9N2, H7N7, H6N1 H7N9, H5N6, and H10N8, have been reported in countries in which these subtypes of avian influenza virus are circulating in poultry. Among these emerging influenza viruses, 650 human infections with H5N1 virus have since been identified from 16 countries, among these 386 were fatal (see, world wide website: who.int/influenza/human_animal_interface/EN_GIP_20140124 CumulativeNumberH5N1cases.pdf?ua=1). Most recently, the emergence of H7N9 virus in China in 2013 has caused 450 human cases, 165 of which were fatal (http://www.who.int/influenza/human_animal_interface/influenza_h7n9/riskassessment_h7n9_27june14.pdf).
Human infections with other novel subtypes of avian influenza virus, such as H10N8 and H5N6, were also reported in China. There is a concern that some of these subtypes may gain further adaptation in humans or become reassortant with seasonal flu virus and cause a new pandemic. The experience of the 2009 pandemic of H1N1 showed preparation of vaccine for human vaccination from the emergence of a virus takes more than 6 months before availability to the public. Current flu vaccine development will not meet the requirement for the nature of rapid dissemination of pandemic influenza. It is a certainty that there will be new pandemics in the future; however, it is impossible to predict the timing and subtype of virus.
Novel live attenuated influenza (flu) vaccines would meet the requirements for seasonal and pandemic vaccines. Live attenuated flu vaccines have several advantages over the split or inactivated vaccines. Firstly, live attenuated vaccines are able to induce better immune response in recipients; secondly, live attenuated vaccines use less vaccine for immunization; finally, attenuated live flu vaccines can be easily applied through nasal administration.